1. Field of Invention
The present invention is generally directed toward a surgical bioactive glass bone implant product and more specifically is a moldable and shapeable putty composition sterilized by gamma radiation for filling bone defects having a bioactive glass material with a size ranging from 32 to 710 μm with a weight ranging from 68% to 76% by weight of the composition mixed in a fluid carrier of glycerol and polyethylene glycol.
2. Background of the Invention
Surgical implants should be designed to be biocompatible in order to successfully perform their intended function. Biocompatibility may be defined as the characteristic of an implant acting in such a way as to allow its therapeutic function to be manifested without secondary adverse affects such as toxicity, foreign body reaction or cellular disruption.
Formable compositions are used to correct surgical defects that may be caused by trauma, pathological disease, surgical intervention or other situations where defects need to be managed in osseous surgery. It is important to have the defect filler in the form of a stable, viscous formable composition to facilitate the placement of the composition into the surgical site which is usually uneven in shape and depth. The surgeon will take the composition on a spatula or other instrument and trowel it into the site or take it in his/her fingers to shape the bone defect material into the proper configuration to fit the site being corrected. It is also important that the defect filler be biocompatible.
Osteogenic bone grafting materials may generally be separated into two classes, namely those which are osteoconductive, and those which are osteoinductive. It can be said that osteoconductive implants “conduct” bone growth across defects when implanted into osseous tissue. Osteoinductive implants, on the other hand, have the ability to “induce” cells in the area to generate bone of their own accord. These osteoinductive implants will cause the generation of bone even when they are implanted into non-osseous tissue.
Many products have been developed in an attempt to treat this surgical need for a biocompatible formable material. One such example is autologous bone particles or segments recovered from the patient. When removed from the patient, the segments or bone particles are wet and viscous from the associated blood. This works very well to heal the defect but requires significant secondary surgery resulting in lengthening the surgery, extending the time the patient is under anesthesia and increasing the cost. In addition, a significant increase in patient morbidity is attendant in this technique as the surgeon must take bone from a non-involved site in the patient to recover sufficient healthy bone, marrow and blood to perform the defect filling surgery. This leads to significant post-operative pain.
Allograft bone is a logical substitute for autologous bone. It is readily available and precludes the surgical complications and patient morbidity associated with autologous bone as noted above. Allograft bone is essentially a collagen fiber reinforced hydroxyapatite matrix containing active bone morphogenic proteins (BMP) and can be provided in a sterile form.
Demineralized Bone Matrix (DBM) was first described by Senn in 1889. It was rediscovered and thoroughly studied by Urist and Strates in the late 19603 s. It has since become a major product of tissue banks around the world. As the name implies, it is bone which has been demineralized by treatment with acid. The demineralized form of allograft bone is naturally both osteoinductive and osteoconductive. The demineralized allograft bone tissue is fully incorporated in the patient's tissue by a well established biological mechanism. It has been used for many years in bone surgery to fill the osseous defects previously discussed.
Demineralized allograft bone is usually available in a lyophilized or freeze dried and sterile form to provide for extended shelf life. The bone in this form is usually very coarse and dry and is difficult to manipulate by the surgeon. One solution to use such freeze dried bone has been provided in the form of a gel, GRAFTON®, a registered trademark of Osteotech Inc., which is a simple mixture of glycerol and lyophilized, demineralized bone powder of a particle size in the range of 0.1 cm to 1.2 cm (1000 microns to 12,000 microns) as is disclosed in U.S. Pat. No. 5,073,373. GRAFTON works well to allow the surgeon to place the allograft bone material at the site.
However, the carrier, glycerol has a very low molecular weight (92 Daltons) and is very soluble in water, the primary component of the blood which flows at the surgical site. Glycerol also experiences a marked reduction in viscosity when its temperature rises from room temperature (typically 22° C. in an operating room) to the temperature of the patient's tissue, typically 37° C. This combination of high water solubility and reduced viscosity causes the allograft bone material with a glycerol carrier to be runny and to flow away from the site almost immediately after placement which prevents the proper retention of the bone material within the site as carefully placed by the surgeon.
U.S. Pat. No. 5,290,558 discloses a flowable demineralized bone powder composition using an osteogenic bone powder with large particle size ranging from about 0.1 to about 1.2 cm mixed with a low molecular weight polyhydroxy compound possessing from 2 to about 18 carbons including a number of classes of different compounds such as monosaccharides, disaccharides, water dispersible oligosaccharides and polysaccharides.
U.S. Pat. No. 5,356,629 discloses making a rigid composition in the nature of a bone cement to fill defects in bone by mixing biocompatible particles preferably polymethylmethacrylate coated with polyhydroxyethylmethacrylate in a matrix selected from a group which lists hyaluronic acid to obtain a molded semi-solid mass which can be suitably worked for implantation into bone. The hyaluronic acid can also be utilized in monomeric form or in polymeric form preferably having a molecular weight not greater than about one million Daltons. It is noted that the nonbioabsorbable material which can be used to form the biocompatible particles can be derived from xenograft bone, homologous bone, autogenous bone as well as other materials. The bioactive substance can also be an osteogenic agent such as demineralized bone powder, in addition to morselized cancellous bone, aspirated bone marrow and other autogenous bone sources. The average size of the particles employed is preferably about 0.1 to about 3.0 mm, more preferably about 0.2 to about 1.5 mm, and most preferably about 0.3 to about 1.0 mm. It is inferentially mentioned but not taught that particles having average sizes of about 7,000 to 8,000 microns, or even as small as about 100 to 700 microns can be used. This is simply a cement used for implantation of hip prosthesis and is not used to promote bone growth.
U.S. Pat. No. 6,437,018 issued Aug. 20, 2002 owned by the assignee of the present invention discloses a malleable bone putty and a flowable gel composition for application to a bone defect site to promote new bone growth at the site using demineralized lyophilized allograft bone powder. The bone powder has a particle size ranging from about 100 to about 850 microns and is mixed in a high molecular weight hydrogel carrier containing a sodium phosphate saline buffer, the hydrogel component of the carrier ranging from about 0.75 to 4.5% of the composition and having a molecular weight of about at least 160,000 Daltons. The composition has a pH between 6.8-7.4, contains about 25% to about 35% bone powder and can be additionally provided with BMP's. Another malleable bone putty is disclosed in U.S. Pat. No. 6,030,635, now RE 38,522, issued Feb. 29, 2000.
Another product group involves the use of inorganic materials to provide a matrix for new bone to grow at the surgical site. These inorganic materials include hydroxyapatite obtained from sea coral or derived synthetically. Either form may be mixed with the patient's blood and/or bone marrow to form a gel or a putty. Calcium sulfate or plaster of Paris may be mixed with water to similarly form a putty. Other products within this group include ceramics such as tricalcium phosphate.
The use of ceramic compositions utilizing beta tricalcium phosphate and alpha tricalcium phosphate (TCP) for bone graft substitutes are also well known in the art. These graft materials generally harden in place. U.S. Pat. No. 5,522,893 issued Jun. 4, 1996 discloses a bone filling material which is a combination of tricalcium phosphate and dicalcium phosphate salts that are mixed and react to harden and form hydroxycarbonate apatite after implantation. The prior art TCP compositions tend to harden rather quickly and have short if any shelf life. Thus, the composition has to be mixed at the time of surgery or in a short time period before the time of surgery.
Bioglass® and other bioactive glass is a bone grafting material composed of SiO2, Na2O, CaO, P2O5 glass which has the ability to produce a bio-active surface layer of hydroxyapatite carbonate within minutes of implantation. This material does not rely on donor availability and overcomes cultural and religious qualms or prohibitions about using human bone. Furthermore, the material has osteoinductive and osteoconductive characteristics and a long shelf life which allow it to be successfully used as bone implant repair material.